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Published on: September 22, 2020
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Characterizing the Immune Response in Pig-to-Human Heart Xenografts Using a Multimodal Diagnostic System
Alessia Giarraputo1, Erwan Morgand1, Jeffrey Stern2
1Université Paris Cité, INSERM U970 PARCC, Paris Institute for Transplantation and Organ Regeneration, Paris, France (A. Giarraputo, E.M., F.M., G.C., V.G., A.S., A.C., P.B., A.L.).
Circulation
|October 2, 2025
Summary
Early pig-to-human heart xenotransplants show mild innate immune responses and endothelial activation. This xenotransplantation study characterized the xenoimmune response in heart grafts, revealing key cellular and molecular signatures.
Area of Science:
- Transplantation immunology
- Xenotransplantation research
- Genomic medicine
Background:
- Genome-edited pigs enable recent pig-to-human heart xenotransplants.
- The xenoimmune response in heart xenografts is not well understood.
- This study characterized the xenoimmune response and injury in pig-to-human heart xenografts.
Purpose of the Study:
- To precisely characterize the xenoimmune response and injury in heart xenografts.
- To analyze xenograft biopsy specimens using multimodal phenotyping.
- To compare xenografts with control pig hearts.
Main Methods:
- Multimodal phenotyping of xenograft biopsy specimens 66 hours post-reperfusion.
- Morphological evaluation, immunophenotyping, ultrastructural assessment.
- Automated quantification of multiplex immunofluorescence and gene expression profiling.
Main Results:
- Xenografts showed endothelial activation and mild microvascular inflammation.
- Immune infiltrates were primarily innate immune cells (CD15+, CD68+).
- Gene expression revealed monocyte/macrophage and neutrophil activation, interferon-gamma response, and endothelial activation.
Conclusions:
- Pig-to-human heart xenografts exhibit early xenoimmune responses.
- Findings suggest mild innate microvascular inflammation and endothelial activation.
- A precision diagnostic system could enhance future graft monitoring.
